Many kinds of protozoa, including the erythrocytic stages of malarial parasites, develop only within a living host cell. Do these organisms gain an energetic advantage by losing or suppressing certain biosynthetic capabilities? Do they parasitize the energy-producing mechanisms of the host cell? How much of the integrity of the host cell do they require? The proposed studies on initial extracellular development of the merozoites of Plasmodium falciparum constitute approaches to finding answers to these questions. Cultures of P. flaciparum developing intracellularly in human erythrocytes maintained in vitro will be used as source of viable merozoites. Such merozoites inoculated into a culture medium containing a 33% human erythrocyte extract show initial differentiation into young ring stages only if the medium is supplemented with ATP and pyruvate. Further work will be directed along 3 lines: 1) to place this phenomenon on a more quantitative basis and to increase the extent of extracellular development; 2) to study in more detail the role of the ATP; 3) to examine the possible role of proteinkinase activators in differentiation of the erythrocytic stages of P. falciparum. The information obtained will bear on fundamental problems in cell biology and will also contribute to understanding of the physiology of the pathogenic erythrocytic stage of malarial parasites, causative agents of a major human disease.